Cardiovascular disease (CVD) is increasing among Alaska Natives. The Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study has been examining CVD and its risk factors by conducting a family genetic study among Eskimos residing in eight villages and the town of Nome in the Norton Sound Region. This application proposes to extend the GOCADAN study to pursue the following aims: 1) Expand the genetic studies that will emphasize the genome scan approach. The completed genome scan of 1214 members who are nearly all part of one extended pedigree will be used to identify quantitative trait loci for subclinical CVD and CVD risk factors and narrow the regions of interest by fine mapping. 2) Re-examine the family members so that changes in risk factors can be analyzed and genetic effects on changes estimated. Surveillance for CVD events will be instituted, including annual mortality surveillance and follow-up of nonfatal events uncovered at the time of the re-exam. Advantages of GOCADAN include: 1) It provides health data on an underserved ethnic group. 2) The large extended pedigree improves the chances of detecting significant loci for subclinical CVD and its risk factors. 3) Data from carotid ultrasound measures will improve understanding of mechanisms of vascular disease and the genetics of CVD. 4) A unique constellation of risk factors with low rates of several risk factors, such as diabetes and hypertension, but high levels of inflammation and rates of smoking, provides a population uniquely suited to examine the roles of inflammatory markers in CVD. GOCADAN will lead to valuable therapeutic and prevention strategies for this and other populations in the United States and the world, where the epidemics of obesity, diabetes, and CVD are increasing rapidly.